Retrovirus-specific differences in matrix and nucleocapsid protein-nucleic acid interactions: implications for genomic RNA packaging

J Virol. 2014 Jan;88(2):1271-80. doi: 10.1128/JVI.02151-13. Epub 2013 Nov 13.

Abstract

Retroviral RNA encapsidation involves a recognition event between genomic RNA (gRNA) and one or more domains in Gag. In HIV-1, the nucleocapsid (NC) domain is involved in gRNA packaging and displays robust nucleic acid (NA) binding and chaperone functions. In comparison, NC of human T-cell leukemia virus type 1 (HTLV-1), a deltaretrovirus, displays weaker NA binding and chaperone activity. Mutation of conserved charged residues in the deltaretrovirus bovine leukemia virus (BLV) matrix (MA) and NC domains affects virus replication and gRNA packaging efficiency. Based on these observations, we hypothesized that the MA domain may generally contribute to NA binding and genome encapsidation in deltaretroviruses. Here, we examined the interaction between HTLV-2 and HIV-1 MA proteins and various NAs in vitro. HTLV-2 MA displays higher NA binding affinity and better chaperone activity than HIV-1 MA. HTLV-2 MA also binds NAs with higher affinity than HTLV-2 NC and displays more robust chaperone function. Mutation of two basic residues in HTLV-2 MA α-helix II, previously implicated in BLV gRNA packaging, reduces NA binding affinity. HTLV-2 MA binds with high affinity and specificity to RNA derived from the putative packaging signal of HTLV-2 relative to nonspecific NA. Furthermore, an HIV-1 MA triple mutant designed to mimic the basic character of HTLV-2 MA α-helix II dramatically improves binding affinity and chaperone activity of HIV-1 MA in vitro and restores RNA packaging to a ΔNC HIV-1 variant in cell-based assays. Taken together, these results are consistent with a role for deltaretrovirus MA proteins in viral RNA packaging.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Cattle
  • HIV Antigens / chemistry
  • HIV Antigens / genetics
  • HIV Antigens / metabolism*
  • HIV Infections / virology*
  • HIV-1 / chemistry
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • HTLV-II Infections / virology*
  • Human T-lymphotropic virus 2 / chemistry
  • Human T-lymphotropic virus 2 / genetics
  • Human T-lymphotropic virus 2 / physiology*
  • Humans
  • Nucleocapsid Proteins / chemistry
  • Nucleocapsid Proteins / genetics
  • Nucleocapsid Proteins / metabolism*
  • Protein Binding
  • Protein Structure, Secondary
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*
  • Sequence Alignment
  • Species Specificity
  • Virus Assembly*
  • gag Gene Products, Human Immunodeficiency Virus / chemistry
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • HIV Antigens
  • Nucleocapsid Proteins
  • RNA, Viral
  • gag Gene Products, Human Immunodeficiency Virus
  • p17 protein, Human Immunodeficiency Virus Type 1